Although the consumption of long chain polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has long been recognized as providing a variety of health benefits, until very recently the consumption of their monounsaturated equivalents was thought to be unhealthy. As is stated by Imamura et al, “Long-chain monounsaturated fatty acids and incidence of congestive heart failure in two prospective cohorts”, Circulation, 2013 Apr. 9; 127(14): 1512-1522, “In the 1960s-1980s, feeding experiments in rodents, pigs and non-human primates suggested that consumption of erucic acid (22:1n9) and cetoleic acid (22:1n11) caused cardiac steatosis. Although potential effects in humans were never studied, mechanistic studies suggest that exposure to long-chain monounsaturated fatty acids (LCMUFA. 20:1, 22:1 and 24:1 fatty acids) might impair myocardium”. In this regard, it is noted that lipids are described by the formula X:YnZ wherein X is the number of carbon atoms in their alkyl chain, and Y is the number of double bonds in such chain; and where “Z” is the number of carbon atoms from the methyl end group to the first double bond. In nature the double bonds are all in the cis-form. In polyunsaturated fatty acids each double bond is separated from the next by one methylene (—CH2—) group. Using this nomenclature, EPA is 20:5n3 while DHA is 22:6n3.
After analyzing circulating phospholipid LCMUFA content in patients exhibiting arteriosclerosis or congestive heart failure, Imamura found that increased levels of 24:1 are associated with specific physiologic risk factors as well as with higher incidence of congestive heart failure. Consumption of 22:1 led to some increased risk (as 22:1 is elongated to 24:1); no association was found with respect to 20:1 fatty acids.
Recent research has shown that 20:1 and 22:1 long-chain monounsaturated fatty acids actually possess desirable health effects. Thus Yang et al, Dietary supplementation with long-chain monounsaturated fatty acids attenuates obesity-related metabolic dysfunction and increases expression of PPAR gamma in adipose tissue in type 2 diabetic KK-Ay mice, Nutrition & Metabolism 2013, 10:16 discloses that the dietary treatment of such mice with such long-chain monounsaturated fatty acids improved their diabetic condition.
Unfortunately, recent research has also indicated that combining higher long-chain polyunsaturated fatty acids (LC-PUFAs) such as EPA (20:5) and DHA (22:6) from fish oil with certain monounsaturated fatty acids, such as oleic acid (18:1), from plants may cancel out the health benefits derived from each. Thus Hlais et al, Combined Fish Oil and High Oleic Sunflower Oil Supplements Neutralize the Individual Effects on the Lipid Profile of Healthy Men, Lipids (2013) 48:853-861 conclude that “the impact of oleic acid (n-9) on total and LDL cholesterol was altered by the addition of fish oil (n-3). These effects may have been the result of enzymatic competition between the two types of fatty acids.” (Abstract).
Accordingly, it would be desirable to possess a composition comprising a high concentration of higher long-chain monounsaturated fatty acids (i.e., 20:1 and 22:1), which composition did not contain a substantial amount of higher long-chain polyunsaturated fatty acids as well. One difficulty associated with the production of such a material is that many of the fish species which produce oil having a higher concentration of such higher long-chain monounsaturated fatty acids (for example herring) also produce high concentrations of higher long-chain polyunsaturated fatty acids as well. Interestingly, the reverse is not true—most higher long-chain polyunsaturated fatty acids such as EPA and DHA are isolated from species of fish (primarily anchovy, found off the Western coast of South America) which produce oils having a high long-chain polyunsaturated fatty acid content and a low content of long-chain monounsaturated fatty acids. Thus, for example, Opstvedt, Fish Lipids in Animal Nutrition, Norwegian Herring Oil & Meal Industry Research Industry, Technical Bulletin No. 22, October 1985 reports that Peruvian Anchovy has a 20:5 and 22:6 content of 33.7 (w/w %), but a 20:1+22:1 content of only 2.8%.
Unfortunately, many of the processes typically employed to concentrate fish oil fatty acids, such as short path distillation and supercritical fluid extraction primarily separate fatty acid derivatives based upon variation in chain length rather than saturation. While fractionation methods such as urea fractionation may be employed, such processes are economically unacceptable due to the large amounts of reagent needed, particularly with fish oils which contain large amounts of both long-chain polyunsaturated fatty acids and long-chain monounsaturated fatty acids.
Lithium salts have been employed to separate long-chain polyunsaturated fatty acids from other components of fish oil in the past. Thus, for example, US Patent Application 2013/0150602 (Keliher et al) discloses a process where lithium salts are employed to remove non-acidic impurities from a single fatty acid—rather than separating fatty acids from one another. The non-acidic impurities are typically impurities that are produced during a chemical synthesis of a single fatty acid (see paragraph 44 of 2013/0150602). WO 2011/095284 (Horlacher et al) discloses a process wherein saturated fatty acids are removed from polyunsaturated fatty acids (particularly EPA and DHA) by treating free fatty acids concentrated from fish oils having a high EPA and DHA content with a sodium or lithium salt and ethanol. While the prior art discloses that a lithium salt/acetone fractionation process could be employed, such art indicates that the use of such a process would not be particularly effective. Thus, Fontell et al, Some new method for separation and analysis of fatty acids and other lipids, Journal of Lipid Research, Volume 1, Number 5, pages 391-404 (1960) state (on pages 391-392) that “One inherent disadvantage of the method [lithium salt/acetone fractionation] is the co-crystallization of fatty acids, which leads to less perfect separations than solubility data would predict. While it is normally possible to obtain quite good separation of saturated from unsaturated fatty acids by this method, a separation of monoene from polyene acids is less precise . . . ”
Accordingly, it is completely unexpected that a lithium fractionation employing an organic solvent such as ethanol and/or acetone could be used to separate long-chain monounsaturated fatty acids from long-chain polyunsaturated fatty acids in compositions comprising a high concentration of both such materials.